Phosphorus oxychloride → 1,4-Dichloro-7-(3-cyanophenyl)isoquinoline

HRID 479565Notes

Reaction equation

HRID 479565 reaction equation
O=P(Cl)(Cl)[Cl:3].[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=3)=[CH:14][CH:15]=2)[C:10](=O)[NH:9][CH:8]=1>CC#N>[Cl:3][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=3)[CH:12]=2)[C:7]([Cl:6])=[CH:8][N:9]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 534397463-(4-Chloro-1-oxo-1,2-dihydroisoquinolin-7-YL)benzonitrile

Product 1

HCID 187712921,4-Dichloro-7-(3-cyanophenyl)isoquinolineYield 88.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of POCl3 (8.36 kg, 54.5 mol) in MeCN (11.5 L) was added to a suspension of 4-chloro-7-(3-cyanophenyl)isoquinolinone (7.65 kg, 27.3 mol) in boiling MeCN (65 L) under N2 over 1 hour. The mixture was heated at reflux for 11 hours and then cooled to room temperature. The mixture was slowly quenched with 1N aqueous HCl (38.3 L) and the resultant slurry stirred for 1 hour. The solid was collected by filtration, washed with MeCN (7.6 L) and dried in vacuo at 50° C. to give 1,4-dichloro-7-(3-cyanophenyl)isoquinoline (7.20 kg, 24.1 mol, 88%) as a creamy coloured solid.

Workup

  1. customover 1 hour
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 11 hours
  4. customThe mixture was slowly quenched with 1N aqueous HCl (38.3 L)
  5. filtrationThe solid was collected by filtration
  6. washwashed with MeCN (7.6 L)
  7. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-22c7ffc8c6ba44578260f331c30d8a9c
Source dataset
uspto-grants-2003_11
Patent number
US06645979B2

Reaction notes

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